Physiology and Pharmacology

en Intraperitoneal Carbamylated erythropoietin improves memory and hippocampal apoptosis in beta-amyloid rat model of Alzheimer’s disease through stimulating autophagy and inhibiting necroptosis Nervous system (others) Others Experimental research article Experimental research article <div style="text-align: justify;"><strong>Introduction:</strong> Alzheimer’s disease (AD) is marked by the deposition of amyloid-β (Aβ) plaques and tau tangles. Although Erythropoietin (EPO) provides neuroprotective and memory-improving properties, its application has been limited due to the hematopoietic effects. Carbamylated Erythropoietin-Fc (CEPO-Fc) was developed as a non-erythropoietic EPO derivative that possesses neuroprotective potential. However, the molecular mechanisms behind the protective effects of CEPO-Fc’s in AD are still under consideration. Therefore, herein investigated the therapeutic properties of intraperitoneal (i.p.) dose of CEPO-Fc on Aβ-induced neurotoxicity in adult male Wistar rats. <strong>Methods:</strong> The rats received microinjections of Aβ25-35 (5 μg/2.5 μl, per side) in the dorsal hippocampus for four consecutive days. CEPO-Fc was injected intraperitoneally in two doses of 500 and 5000 IU during the next six days. Learning and memory performance were studied (days 10-13) using the Morris Water Maze task. Immunoblotting was also undertaken to assess the molecular levels of leading indicators of apoptosis (Bax, Bcl-2, and caspase-3), necroptosis (Phosphorylated-Receptor-interacting serine/threonine-protein kinase 3 (p-RIP3)), as well as autophagy (phosphorylated-Beclin-1 (p-Beclin-1) and phosphorylated-1A/1B-light chain 3 (p-LC3-II)) in the hippocampus. <strong>Results:</strong> Behavioral analysis indicated that CEPO-Fc 500 and 5000 IU reversed memory impairment. Moreover, the hippocampus’s molecular study showed upregulation of P-LC3-II/LC3-II and suppression of Bax/Bcl-2, Caspase-3, and P-RIP3/RIP3 processes. <strong>Conclusion: </strong>Our findings imply that the neuroprotective characteristics of CEPO-Fc in the AD rats are mediated through autophagy activation and regulation of apoptosis and necroptosis processes. These results suggest that an i.p. dose of CEPO-Fc could be used to protect against AD-induced neurotoxicity.</div> Apoptosis, Autophagy, Alzheimer’s disease, Necroptosis, Carbamylated Erythropoietin-Fc 395 411 http://ppj.phypha.ir/browse.php?a_code=A-10-1604-2&slc_lang=en&sid=1 Amirhossein Maghsoudi 3200319475328460031573 3200319475328460031573 No Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Jalal Zaringhalam jzaringhalam@sbmu.ac.ir 3200319475328460031574 3200319475328460031574 Yes Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran Maryam Moosavi 3200319475328460031575 3200319475328460031575 No Nanomedicine and Nanobiology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran Akram Eidi 3200319475328460031576 3200319475328460031576 No Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran